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MicroRNAs in Parkinson's disease: From pathogenesis to diagnostics and therapeutic strategies

2 months 3 weeks ago
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by pathological changes, including the loss of dopaminergic neurons and abnormal aggregation of α-synuclein (α-syn). Certain cellular and molecular events are involved; however, the origin and significance of these events remain uncertain. The discovery of microRNAs (miRNAs) predicted to play a pivotal role in various regulatory processes has emerged. Studies on the dysregulation of miRNAs in PD pathogenesis,...
Dongying Zheng

Astrocyte-to-neuron H(2)O(2) signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer's disease model

2 months 3 weeks ago
Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron H(2)O(2) signalling cascade in Drosophila that is essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an increase in intracellular calcium...
Yasmine Rabah

The effect of distraction and feedback on prefrontal cortex activity and balance in middle-aged adults: A functional near-infrared spectroscopy pilot study

2 months 3 weeks ago
Maintaining balance while simultaneously performing other tasks is common during everyday activities. However, this dual-tasking (DT) divides attention and increases cognitive demand, which can be detrimental to stability in older adults. It is unknown if the focus of attention influences how a dual-task affects balance and whether this is detectable in middle-aged adults. This study investigates the effect of dual-task and attentional focus on prefrontal cortex (PFC) activity in young (YA) and...
L Maureen Krelove

Specific types of male infertility are correlated with T cell exhaustion or senescence signatures

2 months 3 weeks ago
The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men....
Giada Amodio

Mechanisms of RCD-1 pore formation and membrane bending

2 months 3 weeks ago
Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds...
Keli Ren

Lipid-induced condensate formation from the Alzheimer's Abeta peptide triggers amyloid aggregation

2 months 3 weeks ago
The onset and development of Alzheimer's disease is linked to the accumulation of pathological aggregates formed from the normally monomeric amyloid-β peptide within the central nervous system. These Aβ aggregates are increasingly successfully targeted with clinical therapies at later stages of the disease, but the fundamental molecular steps in early stage disease that trigger the initial nucleation event leading to the conversion of monomeric Aβ peptide into pathological aggregates remain...
Greta Šneiderienė

Age, cancer, and the dual burden of cancer and doxorubicin in skeletal muscle wasting in female rats: which one to blame?

2 months 3 weeks ago
Sarcopenia and cancer cachexia are two life-threatening conditions often misdiagnosed. The skeletal muscle is one of the organs most adversely affected by these conditions, culminating in poor quality of life and premature mortality. In addition, it has been suggested that chemotherapeutic agents exacerbate cancer cachexia, as is the case of doxorubicin. Herein, we sought to investigate markers of inflammation and neuromuscular junction (NMJ) remodeling during aging and in response to cancer or...
Alexandra Moreira-Pais

Sestrin2 ameliorates age-related spontaneous benign prostatic hyperplasia via activation of AMPK/mTOR dependent autophagy

2 months 3 weeks ago
Benign prostatic hyperplasia (BPH), characterized as a chronic disease with unregulated enlargement of prostatic gland, is commonly observed in elderly men leading to lower urinary tract dysfunction. Sestrin2 plays a role in the maintenance of cellular homeostasis and protects organisms from various stimuli. The exact role of Sestrin2 in the etiology of BPH, a common age-related disease, remains unknown. Here, we explored the regulatory function of Sestrin2 in modulating autophagy and its...
Hui-Ju Lee

Comprehensive evaluation of lifespan-extending molecules in C. elegans

2 months 3 weeks ago
The nematode C. elegans has long served as a gold-standard model organism in aging research, particularly since the discovery of long-lived mutants in conserved aging pathways including daf-2 (IGF1) and age-1 (PI3K). Its short lifespan and small size make it highly suitable for high-throughput experiments. While numerous molecules have been tested for their effects on C. elegans lifespan, consensus is still lacking regarding the most effective and reproducible compounds. Confounding effects,...
Grace B Phelps

Optimising Age-Specific Insulin Signalling to Slow Down Reproductive Ageing Increases Fitness in Different Nutritional Environments

2 months 3 weeks ago
The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of Caenorhabditis elegans at the cost of reduced reproduction. Here, we show that...
Zahida Sultanova

rDNA Copy Number Variation and Methylation During Normal and Premature Aging

2 months 3 weeks ago
Ribosomal RNA is the main component of the ribosome, which is essential for protein synthesis. The diploid human genome contains several hundred copies of the rDNA transcription unit (TU). Droplet digital PCR and deep bisulfite sequencing were used to determine the absolute copy number (CN) and the methylation status of individual rDNA TU in blood samples of healthy individuals. The absolute CN ranged from 243 to 895 (median 469). There was no difference in absolute CN between males and females...
Alva B C Geisen

Lifetime age-related changes in clinical laboratory results, aging clocks and mortality predictors in 2412 Golden Retrievers

2 months 3 weeks ago
In this study, we investigated age-related changes in clinical laboratory data and their association with mortality in dogs from the Golden Retriever Lifetime Study. By analyzing complete blood count (CBC) and biochemistry data from 2'412 Golden Retrievers over 16,678 visits, we observed significant changes during the first 2 years of life and throughout aging. Based on these observations, we developed a biological aging clock using a LASSO model to predict age based on blood markers, achieving...
Kevin Perez

Life history is a key driver of temporal fluctuations in tropical tree abundances

2 months 3 weeks ago
The question of what mechanisms maintain tropical biodiversity is a critical frontier in ecology, intensified by the heightened risk of biodiversity loss faced in tropical regions. Ecological theory has shed light on multiple mechanisms that could lead to the high levels of biodiversity in tropical forests. But variation in species abundances over time may be just as important as overall biodiversity, with a more immediate connection to the risk of extirpation and biodiversity loss. Despite the...
Kenneth Jops

A tough soft-hard interface in the human knee joint driven by multiscale toughening mechanisms

2 months 3 weeks ago
Joining heterogeneous materials in engineered structures remains a significant challenge due to stress concentration at interfaces, which often leads to unexpected failures. Investigating the complex, multiscale-graded structures found in animal tissue provides valuable insights that can help address this challenge. The human meniscus root-bone interface is an exemplary model, renowned for its exceptional fatigue resistance, toughness, and interfacial adhesion properties throughout its lifespan....
Wenyue Li